小鼠足容积的活体和离体测量

本实验建立小鼠足容积测量方法学并提供小鼠足容积的生理数值，为进一步研究实验性皮肤癌发生的免疫机制打下基础．根据毛细管放大原理，使用自制的小鼠足容积测量仪测量３５１只昆明种小鼠左右足容积，发现左右足容积几乎相等．另对１５０只小鼠左右足进行３６９次重复测量，发现合格测量超过９７％．不同体重小鼠足生长曲线研究表明，随着体重的增加，小鼠足容积渐趋于一定值，表明生长停止．并且体重２５ｇ以上小鼠活体离体足容积差接近一定值，这提示大龄小鼠足血管张力和容积基本恒定．     

Double nondisjunction during karyotypic progression of chemically induced Syrian hamster cell lines

The karyotypic evolution of three chemically induced cell lines of Syrian hamster embryo in culture are described. The only karyotypic alteration of one clone was a trisomy of chromosome #11, which presumably arose by nondisjunction after carcinogen treatment. A pure population of cells with the trisomy was observed repeatedly upon karyotyping of cells at the first three passages after cloning. However, at a late passage, apparently normal diploid cells appeared in the culture, which we propose resulted from a second nondisjunction of one chromosome #11, reverting the cells from trisomy 11 to disomy 11. The karyotypic evolution of two other cell lines also involved double nondisjunction, which resulted in duplication of a translocated chromosome and concurrent loss of the normal nonrearranged chromosome. Taken together with the reported findings of others, the results indicate that double nondisjunction is a mechanism in karyotypic progression during neoplastic development.     

The relationship between epithelial Ia expression and the inflammatory cell infiltrate during experimental oral carcinogenesis

Summary The development of oral epithelial expression of Ia antigens and its relationship to the presence of IL-2r⁺ (CD25⁺) cells was investigated in rats treated with the water soluble carcinogen 4-nitroquinoline-N-oxide (4NQO). Acetone fixed frozen sections of the palate and tongue were stained using an indirect immunoperoxidase technique and monoclonal antibodies to rat Ia (I-A & I-E) and IL-2 receptor. After 4 weeks 4NQO treatment all rats expressed oral epithelial Ia but thereafter (2–9 months) expression was present in only 20–40% of animals. Epithelial expression of Ia by histologically normal, dysplastic and neoplastic epithelium was always associated with the presence of an underlying inflammatory cell infiltrate containing CD25⁺ cells. Overall there were significantly more CD25⁺ cells in tissue specimens containing Ia⁺ epithelium compared with Ia^– epithelium. Furthermore, during the first 4 weeks of carcinogen treatment, a significant positive correlation was found between the CD25⁺ cell density and occurrence of focal epithelial Ia expression. These results, together with analysis of the T cell, NK cell, macrophage and B cell content of the infiltrates induced by 4NQO, suggest that the CD25⁺ cells represent activated T cells. Thus, our results in this experimental model are consistent with the idea that epithelial expression of Ia is the result of production of IFN- by locally activated T cells.     

桥本氏甲状腺炎并发甲状腺癌的临床病理学研究

目的 探讨桥本氏甲状腺炎并发甲状腺癌的临床病理学特征和癌发生的病理学基础。方法 采用HE染色和免疫组化法观察16例桥本氏甲状腺合并甲状腺癌和12例单纯甲状腺癌的病理学形态和基因蛋白的表达。结果 桥本氏甲状腺合并甲状腺主要为乳头状癌。镜下可见淋巴组织增生病变区甲状腺滤泡上皮细胞不典型增生,中度表达p53、Ki67、bcl-2和c-erbB-2,与癌组织的表达无显著差异（P＞0．05）,而极显著高于非甲状腺炎的癌旁组织（P＜0．01）。结论 桥本氏甲状腺炎合并甲状腺可能是在多基因协同作用下,残存的滤泡上皮细胞发生不典型增生而癌变。     

UVA-induced tumours in pigmented hairless mice and the carcinogenic risks of tanning with UVA

Summary An animal experiment is presented in which two groups of pigmented hairless mice were exposed daily to suberythemal doses of UVA to study tumourigenesis. The aim of the study was to estimate the carcinogenic risks of tanning by UVA. The pigmented hairless mice, Skh-hr2, were separated by selective breeding into two groups, the browns and the blacks. Both groups were exposed daily to UVA from fluorescent UVA lamps (Philips TL40W/09) purified by rigorously filtering out the shorter wavelengths. No acute actinic damage was observed after any exposure. However, in most UVA exposed animals, especially in the blacks, a marked scratching preceded the development of tumours. Hyperkeratosis was also observed. All animals developed tumours. Histopathologically at least 60% of the tumours were squamous cell carcinomas. Depositions of melanophages were observed, but no melanomas. It is beyond any doubt that UVA is carcinogenic in laboratory animals. The present state of knowledge justifies no preference for tanning with UVA over tanning with UVB.     

Lanzoprazole promotes gastric carcinogenesis in rats with duodenogastric reflux

Background Duodenogastric reflux is known to cause an increased frequency of cancer in the glandular portion of the stomach in rats. Furthermore, it is debated whether inhibition of gastric acid secretion may promote gastric carcinogenesis. In the present study we examined the combined effect of gastroduodenal reflux and acid inhibition with respect to the development of gastric carcinoma in the rat.Methods Following the construction of a gastrojejunostomy in male Wistar rats, half of them were given the proton pump inhibitor lanzoprazole for 1 year. The rats were then killed and the pH in the stomach and gastrin in blood were measured. The stomach was examined macroscopically as well as histologically.Results Gastrin levels at autopsy were significantly increased in treated rats compared to the control group, confirming an effect of lanzoprazole on gastric acid secretion. Body weight was significantly reduced in the treated rats. Thirty of 79 rats developed gastric cancer, and they were all adenocarcinomas of the Lauren intestinal type. Gastric cancers occurred significantly more often in lanzoprazole-treated rats (50%) compared with controls (27%).Conclusion Lanzoprazole given orally enhances the carcinogenic effect of duodenogastric reflux in rats.     

大鼠肺鳞癌发生发展过程中肿瘤血管生成及血液供应研究

目的　探讨肺癌发生发展过程中肿瘤血管生成和血液供应 ,以及血管内皮细胞生长因子(VEGF)及其受体Flk 1与肿瘤血管生成的关系。方法　 10 0只Wistar大鼠左肺下叶支气管灌注致癌质碘油 ,分批处死获取肺鳞癌癌变及进展期病变标本 ,使用油画颜料染成黄、绿两种颜色的液态硅橡胶分别灌注支气管动脉与肺动脉 ,免疫组化检测病变组织中VEGF、Flk 1的表达及vWF染色切片上的微血管密度 (MVD)。结果　经支气管动脉灌注黄色液态硅橡胶显示 ,肿瘤病灶呈黄色的新生血管团与曲张的支气管动脉相连通 ,镜下见癌巢间质肿瘤微血管腔充盈硅橡胶颗粒 ;经肺动脉灌注绿色液态硅橡胶 ,肿瘤区绿色的血管呈不连续的枯树枝、断枝、残枝状 ,与肿瘤血管不连续 ,镜下肿瘤微血管腔无硅橡胶颗粒。原位癌的MVD计数 ( 3 9.5 0± 12 .60 )与不典型增生 ( 8.92± 3 .80 )及侵袭癌 ( 61.0 5± 19.92 )比较 ,差异均有显著性 (P <0 .0 1)。从支气管粘膜上皮增生→鳞状化生→不典型增生→原位癌→侵袭癌 ,VEGF和Flk 1阳性系数逐渐升高。MVD与VEGF和Flk 1表达均呈正相关 (r分别为 0 .9798和 0 .90 78,P <0 .0 0 5 )。结论　肺癌新生血管形成是大鼠肺鳞癌发生发展的重要现象 ,新生的肿瘤血管与支气管动脉相连通 ,与肺动脉不相连通 ,证明肺鳞癌发生     

mRNA EXPRESSION OF PTEN AND VEGF GENES IN EPITHELIAL OVARIAN CANCER

VEGF gene, also known as vascular permeability factor, has been mapped to chromosome 6p21.3[11]. Biochemically, it is a heparin binding glycoprotein that has in at least four molecular isoforms, among which, VEGF165 occurs most common. VEGF can act as a specific mitogen for a variety of endothelial cells in vitro and as an angiogenic molecule in vivo [11,12]. VEGF is a potent multifunctional cytokine that exerts several potentially independent actions on the vascular endothelium, includin…     

Polymorphisms of interleukin (IL)-1α, IL-1β, IL-6, IL-10, and IL-18 and the risk of ovarian cancer

OBJECTIVE: Recent studies of ovarian cancer have suggested a role for inflammation in carcinogenesis. Data from a population-based case-control study in Hawaii were examined to assess the relation between polymorphisms in cytokines involved with the inflammatory response, specifically members of the interleukin (IL) family and the incidence of ovarian cancer. PATIENTS AND METHODS: The analysis of 182 epithelial ovarian cancer cases and 219 controls focused on the polymorphisms in the following genes: IL-1alpha, IL-1beta, IL-6, IL-10, and IL-18. Genotype data were obtained from blood samples collected in participants' homes, and reproductive, demographic, and lifestyle histories were collected during interview. RESULTS: There were no significant odds ratios (ORs) for ovarian cancer by allelic variants in any of the IL genes after adjusting for age, ethnicity, education, oral contraceptive pill use, pregnancy, and history of tubal ligation. Although there was a significantly reduced risk of ovarian cancer risk among women with an IL-1alpha (-4845) T allele compared to women with two G alleles (OR: 0.59; 95% confidence interval: 0.37-0.97) after adjustment for age and ethnicity, the trend was not significant (p = 0.10). Further examination of the data suggested that women with at least one IL-18 variant allele (a G to C transition at position -137) were at significantly decreased risk of advanced ovarian cancer (OR: 0.51; 95% confidence interval: 0.28-0.90) compared to women with the IL-18 GG genotype. There was a significant difference in the risk of ovarian cancer associated with the IL-18 C allele by stage at diagnosis (p = 0.04 for homogeneity in the ORs): cases with IL-18 GC or CC genotypes were less likely to be diagnosed at regional/distant stages. Analysis of the data within ethnic subgroups revealed a significant positive association of the heterozygous IL-18 GC genotype with ovarian cancer risk among Native Hawaiian women (OR: 9.96; 95% CI: 1.88-52.90). The OR for ovarian cancer was not significant for Native Hawaiian women homozygous for the IL-18 C allele, but only one case and control had the IL-18 CC genotype. CONCLUSIONS: Overall, this study does not support an association of selected IL-1alpha, IL-1beta, IL-6, IL-10, or IL-18 polymorphisms with the risk for ovarian cancer. However, the IL-18 G137C variant may be a marker for ovarian cancer progression or metastasis.     

Ski: Double roles in cancers

The Ski (Sloan-Kettering Institute) is an evolutionarily conserved protein that plays a dual role as an oncoprotein and tumor suppressor gene in the development of human cancer. The Ski oncogene was first identified as a transforming protein of the avian Sloan-Kettering retrovirus in 1986. Since its discovery, Ski has been identified as a carcinogenic regulator in a variety of malignant tumors. Later, it was reported that Ski regulates the occurrence and development of some cancers by acting as an oncogene. Ski mediates the proliferation, differentiation, metastasis, and invasion of numerous cancer cells through various mechanisms. Several studies have shown that Ski expression is correlated with the clinical characteristics of cancer patients and is a promising biomarker and therapeutic target for cancer. In this review, we summarize the mechanisms and potential clinical implications of Ski in dimorphism, cancer occurrence, and progression in various types of cancer.